{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:52:14Z","timestamp":1785523934438,"version":"3.56.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province","doi-asserted-by":"publisher","award":["823RC603)"],"award-info":[{"award-number":["823RC603)"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Industry Research Projects of Hainan Province","award":["(22A200319"],"award-info":[{"award-number":["(22A200319"]}]},{"name":"Health Science and Technology Innovation joint project of Hainan Province","award":["WSJK2024MS230"],"award-info":[{"award-number":["WSJK2024MS230"]}]},{"name":"Health Industry Research Projects of Hainan Province","award":["20A200456"],"award-info":[{"award-number":["20A200456"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      (\n                      <jats:italic>H. pylori<\/jats:italic>\n                      ) infection is the principal etiological factor for gastric cancer (GC), which ranks as the fourth leading cause of cancer-related mortality globally. Although the Correa cascade describes the stepwise progression from chronic gastritis to intestinal-type GC, the molecular events underlying this \u201cinflammation-to-cancer\u201d transition remain incompletely characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to delineate stage-specific proteomic alterations across\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -associated gastric mucosal lesions and to identify candidate progression-associated biomarkers in GC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Label-free quantitative proteomic analysis (LC-MS\/MS) was performed on gastric tissue specimens from 22 patients stratified into four histopathological stages:\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -negative chronic non-atrophic gastritis (HpN-CG),\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -positive chronic non-atrophic gastritis (HpC-CG),\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -positive chronic atrophic gastritis (HpC-CAG), and intestinal-type GC. Functional enrichment (GO, KEGG), temporal clustering (Mfuzz), and protein-protein interaction (PPI) network analyses were conducted. Key hub genes were externally assessed using GEPIA RNA-seq data from TCGA and GTEx.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 6,019 proteins were quantified. Differential expression analysis identified 771 DEPs between HpC-CG and HpN-CG, 101 DEPs between HpC-CAG and HpC-CG, and 535 DEPs between GC and HpC-CAG. Immune response pathways were up-regulated upon\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection, whereas oxidative phosphorylation was progressively suppressed throughout disease progression. Mfuzz clustering revealed that Cluster 4 ribosome-biogenesis proteins, including NIP7 and PDCD11 identified in the proteomic\/PPI analysis, exhibited continuous up-regulation from precancerous stages to GC. External RNA-expression validation supported significant up-regulation of seven Cluster 4 hub genes, whereas Cluster 6 proteins did not show concordant transcript-level down-regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides a comprehensive proteomic landscape of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -driven gastric carcinogenesis. Cluster 4 ribosome-biogenesis proteins represent candidate progression-associated protein markers requiring further protein-level validation, while the progressive decline in oxidative phosphorylation underscores mitochondrial dysfunction as a hallmark of disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353347","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:29:41Z","timestamp":1785518981000},"page":"e0353347","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The quantitative proteomics analysis of multi-stage gastric mucosal lesions associated with Helicobacter pylori infection"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1548-2335","authenticated-orcid":true,"given":"Xiaoxi","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-9418","authenticated-orcid":true,"given":"Jiamei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yening","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"3","key":"pone.0353347.ref001","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"3","key":"pone.0353347.ref002","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/jgh.15751","article-title":"Prevalence of Helicobacter pylori infection in China: A systematic review and meta-analysis","volume":"37","author":"S Ren","year":"2022","journal-title":"J Gastroenterol Hepatol"},{"issue":"2","key":"pone.0353347.ref003","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.canlet.2013.08.016","article-title":"Helicobacter pylori-induced gastric inflammation and gastric cancer","volume":"345","author":"F Wang","year":"2014","journal-title":"Cancer Lett"},{"issue":"10","key":"pone.0353347.ref004","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1002\/cam4.3892","article-title":"Chinese and global burdens of gastric cancer from 1990 to 2019","volume":"10","author":"Y He","year":"2021","journal-title":"Cancer Med"},{"issue":"10258","key":"pone.0353347.ref005","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Global burden of 369 diseases and injuries in 204 countries and territories","year":"2020","journal-title":"Lancet"},{"key":"pone.0353347.ref006","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1479-5876-11-58","article-title":"Clinicopathological characteristics and prognostic analysis of Lauren classification in gastric adenocarcinoma in China","volume":"11","author":"M Qiu","year":"2013","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0353347.ref007","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1751-2980.2011.00550.x","article-title":"The gastric precancerous cascade","volume":"13","author":"P Correa","year":"2012","journal-title":"J Dig Dis"},{"issue":"8","key":"pone.0353347.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0255601","article-title":"Predictors for regression and progression of intestinal metaplasia (IM): A large population-based study from low prevalence area of gastric cancer (IM-predictor trial)","volume":"16","author":"N Aumpan","year":"2021","journal-title":"PLoS One"},{"issue":"7","key":"pone.0353347.ref009","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1136\/gutjnl-2016-311685","article-title":"Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial","volume":"67","author":"RM Mera","year":"2018","journal-title":"Gut"},{"key":"pone.0353347.ref010","doi-asserted-by":"crossref","first-page":"120302","DOI":"10.1016\/j.cca.2025.120302","article-title":"Proteomics in decoding cancer: A review","volume":"574","author":"E Gheybi","year":"2025","journal-title":"Clin Chim Acta"},{"key":"pone.0353347.ref011","doi-asserted-by":"crossref","first-page":"113844","DOI":"10.1016\/j.addr.2021.113844","article-title":"High-throughput proteomics and AI for cancer biomarker discovery","volume":"176","author":"Q Xiao","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"pone.0353347.ref012","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13046-018-0825-0","article-title":"Exosomal TRIM3 is a novel marker and therapy target for gastric cancer","volume":"37","author":"H Fu","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"pone.0353347.ref013","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.clinbiochem.2019.11.001","article-title":"Plasma proteomics-based identification of novel biomarkers in early gastric cancer","volume":"76","author":"B Zhou","year":"2020","journal-title":"Clin Biochem"},{"key":"pone.0353347.ref014","doi-asserted-by":"crossref","first-page":"104340","DOI":"10.1016\/j.ebiom.2022.104340","article-title":"Urine proteomic signatures predicting the progression from premalignancy to malignant gastric cancer","volume":"86","author":"H Fan","year":"2022","journal-title":"EBioMedicine"},{"key":"pone.0353347.ref015","article-title":"iProX in 2021: connecting proteomics data sharing with big data","volume":"50","author":"T Chen","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pone.0353347.ref016","article-title":"iProX: an integrated proteome resource","volume":"47","author":"J Ma","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0353347.ref017","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.3390\/ijms24032895","article-title":"Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms","volume":"24","author":"S Salvatori","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0353347.ref018","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jcmgh.2016.12.001","article-title":"The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer","volume":"3","author":"SF Moss","year":"2016","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"pone.0353347.ref019","doi-asserted-by":"crossref","first-page":"2944156","DOI":"10.1155\/2022\/2944156","article-title":"Immunological perspective: Helicobacter pylori infection and gastritis","volume":"2022","author":"H Yang","year":"2022","journal-title":"Mediators Inflamm"},{"issue":"5","key":"pone.0353347.ref020","doi-asserted-by":"crossref","first-page":"189139","DOI":"10.1016\/j.bbcan.2024.189139","article-title":"Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment","volume":"1879","author":"X Wang","year":"2024","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"5","key":"pone.0353347.ref021","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.jcmgh.2022.01.022","article-title":"Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection","volume":"13","author":"AP Gobert","year":"2022","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"pone.0353347.ref022","doi-asserted-by":"crossref","first-page":"215764","DOI":"10.1016\/j.canlet.2022.215764","article-title":"Helicobacter pylori infection induces stem cell-like properties in Correa cascade of gastric cancer","volume":"542","author":"J He","year":"2022","journal-title":"Cancer Lett"},{"issue":"45","key":"pone.0353347.ref023","doi-asserted-by":"crossref","first-page":"12742","DOI":"10.3748\/wjg.v21.i45.12742","article-title":"Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis","volume":"21","author":"MA Valenzuela","year":"2015","journal-title":"World J Gastroenterol"},{"key":"pone.0353347.ref024","doi-asserted-by":"crossref","first-page":"931493","DOI":"10.3389\/fcell.2022.931493","article-title":"Epigenetic regulation of inflammatory signaling and inflammation-induced cancer","volume":"10","author":"SYX Tan","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"pone.0353347.ref025","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1158\/1541-7786.MCR-20-0936","article-title":"L-plastin promotes gastric cancer growth and metastasis in a Helicobacter pylori cagA-ERK-SP1-dependent manner","volume":"19","author":"YS Teng","year":"2021","journal-title":"Molecular Cancer Research"},{"key":"pone.0353347.ref026","article-title":"Role of the tissue factor pathway in the biology of tumor initiating cells","author":"D Garnier","year":"2010","journal-title":"Thromb Res"},{"issue":"1","key":"pone.0353347.ref027","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13045-020-00932-z","article-title":"Beyond thrombosis: the impact of tissue factor signaling in cancer","volume":"13","author":"D Unruh","year":"2020","journal-title":"J Hematol Oncol"},{"issue":"18","key":"pone.0353347.ref028","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1111\/jcmm.15712","article-title":"Quantitative proteomics identified 3 oxidative phosphorylation genes with clinical prognostic significance in gastric cancer","volume":"24","author":"F Su","year":"2020","journal-title":"J Cell Mol Med"},{"issue":"11","key":"pone.0353347.ref029","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.4251\/wjgo.v14.i11.2097","article-title":"Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis","volume":"14","author":"L-H Zhang","year":"2022","journal-title":"World J Gastrointest Oncol"},{"issue":"7","key":"pone.0353347.ref030","doi-asserted-by":"crossref","first-page":"114424","DOI":"10.1016\/j.celrep.2024.114424","article-title":"Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer","volume":"43","author":"H Chen","year":"2024","journal-title":"Cell Rep"},{"issue":"2","key":"pone.0353347.ref031","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/nar\/gkq758","article-title":"The NIP7 protein is required for accurate pre-rRNA processing in human cells","volume":"39","author":"LG Morello","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"pone.0353347.ref032","year":"2026"},{"key":"pone.0353347.ref033","author":"UniProt","year":"2026"},{"issue":"2","key":"pone.0353347.ref034","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nrc.2018.3","article-title":"Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues","volume":"18","author":"J Pelletier","year":"2018","journal-title":"Nat Rev Cancer"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0353347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:29:47Z","timestamp":1785518987000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0353347"}},"subtitle":[],"editor":[{"given":"Khalid","family":"Raza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0353347","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}